dbSNP rs3088190: ART4:p.Leu300Val (chr12-14829418-G-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_021071.4(ART4):c.898C>G(p.Leu300Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,606,268 control chromosomes in the GnomAD database, including 11,176 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.12 ( 1312 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9864 hom. )

Consequence

ART4
NM_021071.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.332

Publications

16 publications found

Variant links:

Genes affected

ART4 (HGNC:726): (ADP-ribosyltransferase 4 (inactive) (Dombrock blood group)) This gene encodes a protein that contains a mono-ADP-ribosylation (ART) motif. It is a member of the ADP-ribosyltransferase gene family but enzymatic activity has not been demonstrated experimentally. Antigens of the Dombrock blood group system are located on the gene product, which is glycosylphosphatidylinosotol-anchored to the erythrocyte membrane. Allelic variants, some of which lead to adverse transfusion reactions, are known. [provided by RefSeq, Jul 2008]

ART4 links:

C12orf60 (HGNC:28726): (chromosome 12 open reading frame 60)

C12orf60 links:

ENSG00000256339 (HGNC:):

ENSG00000256339 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0039037168).

BP6

Variant 12-14829418-G-C is Benign according to our data. Variant chr12-14829418-G-C is described in ClinVar as Benign. ClinVar VariationId is 3060827.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ART4	NM_021071.4 link	c.898C>G	p.Leu300Val	missense_variant	Exon 3 of 3	ENST00000228936.6	NP_066549.2	Q93070

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ART4	ENST00000228936.6 link	c.898C>G	p.Leu300Val	missense_variant	Exon 3 of 3	1	NM_021071.4	ENSP00000228936.4		Q93070

Frequencies

GnomAD3 genomes

AF:

0.120

AC:

18240

AN:

152010

Hom.:

1304

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.0681

Gnomad AMR

AF:

0.226

Gnomad ASJ

AF:

0.0758

Gnomad EAS

AF:

0.0891

Gnomad SAS

AF:

0.0843

Gnomad FIN

AF:

0.158

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0986

Gnomad OTH

AF:

0.114

GnomAD2 exomes

AF:

0.129

AC:

32062

AN:

247736

AF XY:

0.119

show subpopulations

Gnomad AFR exome

AF:

0.118

Gnomad AMR exome

AF:

0.331

Gnomad ASJ exome

AF:

0.0747

Gnomad EAS exome

AF:

0.0844

Gnomad FIN exome

AF:

0.153

Gnomad NFE exome

AF:

0.0939

Gnomad OTH exome

AF:

0.119

GnomAD4 exome

AF:

0.106

AC:

154611

AN:

1454140

Hom.:

9864

Cov.:

AF XY:

0.104

AC XY:

74862

AN XY:

723294

show subpopulations

African (AFR)

AF:

0.117

AC:

3899

AN:

33216

American (AMR)

AF:

0.326

AC:

14161

AN:

43446

Ashkenazi Jewish (ASJ)

AF:

0.0748

AC:

1947

AN:

26018

East Asian (EAS)

AF:

0.0841

AC:

3308

AN:

39352

South Asian (SAS)

AF:

0.0772

AC:

6538

AN:

84716

European-Finnish (FIN)

AF:

0.152

AC:

8059

AN:

53188

Middle Eastern (MID)

AF:

0.0357

AC:

205

AN:

5750

European-Non Finnish (NFE)

AF:

0.0995

AC:

110276

AN:

1108384

Other (OTH)

AF:

0.104

AC:

6218

AN:

60070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

6386

12772

19157

25543

31929

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4238

8476

12714

16952

21190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.120

AC:

18278

AN:

152128

Hom.:

1312

Cov.:

AF XY:

0.125

AC XY:

9295

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.120

AC:

4989

AN:

41504

American (AMR)

AF:

0.227

AC:

3462

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.0758

AC:

263

AN:

3470

East Asian (EAS)

AF:

0.0897

AC:

464

AN:

5174

South Asian (SAS)

AF:

0.0844

AC:

407

AN:

4824

European-Finnish (FIN)

AF:

0.158

AC:

1667

AN:

10554

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0986

AC:

6708

AN:

68012

Other (OTH)

AF:

0.115

AC:

244

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

797

1594

2391

3188

3985

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

194

388

582

776

970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0991

Hom.:

579

Bravo

AF:

0.129

TwinsUK

AF:

0.104

AC:

386

ALSPAC

AF:

0.102

AC:

392

ESP6500AA

AF:

0.115

AC:

508

ESP6500EA

AF:

0.0978

AC:

841

ExAC

AF:

0.123

AC:

14905

Asia WGS

AF:

0.115

AC:

399

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ART4-related disorder

Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.20

(source)

DANN

Benign

0.76

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.022

MetaRNN

Benign

0.0039

MetaSVM

Benign

-0.94

PhyloP100

-0.33

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.61

REVEL

Benign

0.0030

Sift

Benign

0.12

Sift4G

Uncertain

0.027

Vest4

0.035

MPC

0.0097

ClinPred

0.0049

GERP RS

-5.7

gMVP

0.46

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over